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PubMed2000

Comprehensive gene expression profile of the adult human renal cortex: analysis by cDNA array hybridization.

BACKGROUND: Profiling of gene expression in healthy and diseased renal tissue is important for elucidating the pathogenesis of renal diseases. Comprehensive information about the genes expressed in renal tissue is unavailable. The recently developed cDNA array hybridization methodology allows simultaneous monitoring of thousands of genes expressed renal tissue. METHODS: Complex [alpha-33P]-labeled cDNA probes were prepared from histopathologically uninvolved remnants of nine renal tissues obtained by nephrectomy. Each probe was hybridized to a high-density array of 18,326 paired target genes. The radioactive hybridization signals by phosphorimager screens were quantitated by special software. Bioinformatics from public genomic databases were used to assign a chromosomal location of each expressed transcript and gene function. Cluster analysis was used to arrange genes according to the similarity in pattern of gene expression. RESULTS: A total of 7563 different gene transcripts was detected in the nine tissue samples. Approximately 870 of these genes were full-length mRNA human transcripts (HT), and the remaining 6693 were expressed sequence tags (ESTs). The full-length transcripts were classified by function of the gene product and were listed with information of their chromosomal positions. To allow a comparison between gene expression in clinical and experimental studies, the mouse genes with known similar function to the human counterpart were included in the bioinformatics analysis. Cluster analysis of 502 full-length genes that are expressed in four or more renal tissues revealed more than 110 genes that are highly expressed in all the renal specimens. CONCLUSIONS: The presented data constitute a comprehensive preliminary transcriptional map of the adult human renal cortex. The information may serve as a resource for speeding up the discovery of genes underlying human renal disease. The integrated listing of the full-length expressed human and mouse genes is available through e-mail (Abdalla_Rifai@Brown.edu).

Adult↗

PubMed2003

Tolerability and safety of eletriptan in the treatment of migraine: a comprehensive review.

OBJECTIVE: To provide a comprehensive review of the tolerability and safety of eletriptan. Background.-Eletriptan is a potent and selective 5-HT1B/1D agonist that has demonstrated significant efficacy in the acute treatment of migraine in doses of 20 mg, 40 mg, and 80 mg. DESIGN: This review reports the tolerability and safety of eletriptan across a broad spectrum of preclinical studies and clinical trials that collectively included treatment of more than 11 000 subjects and more than 74 000 migraine attacks. RESULTS: In clinical trials, eletriptan was well tolerated and safe across its dosing range of 20 mg to 80 mg. The adverse event profile of eletriptan 20 mg was similar to placebo, while the most commonly used dose, eletriptan 40 mg, has an adverse event profile that is only marginally higher than placebo. Eletriptan was safe and well tolerated regardless of age or gender, and for both short- and long-term treatment. Eletriptan is metabolized primarily by the CYP3A4 enzyme. Coadministration of potent CYP3A4 inhibitors was not associated with clinically meaningful change in eletriptan tolerability or safety in the population included in these clinical trials. The margin of cardiovascular safety for eletriptan was also confirmed by a well-controlled clinical study in which intravenous eletriptan in excess of an 80-mg dose was rapidly infused in patients undergoing coronary angiography; nonetheless, it is recommended that eletriptan not be coadministered with a limited list of 7 potent CYP3A4 inhibitors; in addition, the triptan class in general (including eletriptan) is contraindicated in patients with symptoms or findings consistent with ischemic heart disease or other significant underlying cardiovascular disease. CONCLUSIONS: This comprehensive review found that eletriptan is safe and well tolerated, and that relatively large changes in dose and plasma concentration result in minimal changes in tolerability.

Acute Disease↗

PubMed1995

A comprehensive transfusion medicine curriculum for medical students. Transfusion Medicine Academic Award Group.

BACKGROUND: The Transfusion Medicine Academic Awards (TMAA) program, sponsored by the National Heart, Lung, and Blood Institute, has provided grants to medical schools to help them develop comprehensive curricula in transfusion medicine. In 1989, the TMAA Group published a set of comprehensive curricular goals for teaching transfusion medicine. The medical student portion of this curriculum has now been revised to reflect new developments in transfusion medicine and recent trends in medical school education. STUDY DESIGN AND METHODS: Two medical schools independently revised the 1989 curriculum for their students. Because significant similarities were noted between curricula of the two institutions, the two revisions were combined and submitted to all TMAA institutions for comment. As a result, a revised medical school curriculum was developed and approved by the TMAA Group. RESULTS: The revised curriculum consists of 28 objectives in six major areas of transfusion medicine. It is presented in its entirety in this article. CONCLUSION: The TMAA transfusion medicine curriculum should provide to medical schools a valuable resource for evaluating their teaching of transfusion medicine and should provide to medical school deans and curriculum committees an authoritative source of transfusion medicine expertise.

Autoimmunity↗

PubMed2001

Impact of comprehensive day treatment on societal participation for persons with acquired brain injury.

OBJECTIVES: To evaluate comprehensive day treatment (CDT) for survivors of brain injury by time since injury and to identify outcome predictors. DESIGN: Before and after. SETTING: Rehabilitation center. PARTICIPANTS: Ninety-six program graduates; 17 dropouts with acquired brain injury. INTERVENTIONS: Comprehensive Day Treatment Program: daily group sessions to build cognitive and behavioral skills through a transdisciplinary approach, supportive feedback, and a variety of therapeutic modalities. Obtained outcome measures before and after the program, and at 1-year follow-up. MAIN OUTCOME MEASURES OUTCOME: Independent living status, vocational independence scale at program end and 1-year follow-up; and Rasch-analyzed Mayo-Portland Adaptability Inventory (MPAI-22) and goal attainment scaling (GAS) at program end. PREDICTORS: age, education, severity of initial injury, time since injury, and preadmission MPAI-22. RESULTS: Significant goal achievement on GAS and improvement on MPAI-22; increased societal participation at 1-year follow-up for those treated postacutely and many years after injury: 72% of graduates living independently; 39% working independently, 10% in transitional placements, and 18% in supported or volunteer work. Long-term outcomes were modestly related linearly to preadmission MPAI-22 and nonlinearly to time since injury. CONCLUSIONS: CDT improves societal participation even among persons with a long history of limited participation after brain injury. This de facto extended baseline analysis indicates the effectiveness of CDT and paves the way for randomized control trials of active treatment components. Relationships of predictors to outcomes are not sufficiently strong for patient selection. More effective interventions for vocational reintegration are needed for those most severely disabled after brain injury.

Activities of Daily Living↗

PubMed2001

Comprehensive critical care education is critical to success.

Intensive and high-dependency care is currently receiving considerable attention, not least since the Department of Health review of adult critical care nursing and subsequent proposals for the development of a consistent and comprehensive critical care service (DoH 2000). The report highlights the need for policy changes at all levels and across all disciplines and makes several recommendations that are deemed essential for the future organization and delivery of critical care. Central to the proposed reforms is the availability of a skilled workforce, adequately prepared and appropriately trained to provide specialist care in a variety of settings where acutely ill patients are found. This paper considers the implications of 'comprehensive critical care' for pre- and post-registration nurse education and offers insight into programmes of learning that are tailored to meet the needs of the service and individuals. The paper draws upon three influential and timely publications, namely the Audit Commission report into critical care services, the English National Board (ENB) review of adult intensive/critical and high-dependency care programmes and the United Kingdom Central Council (UKCC) Commission for Education recommendations regarding 'fitness for practice'.

Critical Care↗

PubMed2001

Reading comprehension: a language intervention target from early childhood through adolescence.

Speech-language pathologists (SLPs) play an important role in helping children and adolescents with language impairments to construct meaning from spoken and written language. They work in collaboration with other professionals and families to provide the optimal learning experiences and to introduce strategies for seeking meaning and monitoring understanding. This article describes language intervention techniques to enhance reading comprehension, including the development and enhancement of background knowledge and schemata, vocabulary, knowledge of text structure, and strategy use. The discussion includes suggestions for young children who are developing language comprehension, as well as for elementary students and secondary students who comprehend text with increasing independence.

Adolescent↗

PubMed2001

Comprehensive assessment for dementia: a necessity for differential diagnosis and management.

A fundamental purpose of comprehensive assessment is to identify impaired and spared abilities of the individual with Alzheimer's disease (AD). In the hands of a skilled professional, the results of a comprehensive assessment provide the basis for the design of meaningful care plans, document the need for appropriate services, and result in optimal patient care. To obtain valid test results, clinicians must be able to recognize and, when possible, control the influence of age-associated variables on test performance. Also, clinicians must be knowledgeable about the many purposes of assessment and consider them when selecting appropriate test instruments. Standardized tests are now available that have been designed specifically to assess communicative and cognitive function in persons with dementia of varying severity. In this article, four standardized tests are described, with particular focus on the information they provide about impaired and spared abilities. Measures that have been found to be useful in screening for the presence of dementia also are discussed.

Age Factors↗

PubMed2001

Comprehensive approach to rejuvenation of the neck.

A comprehensive rejuvenation of the neck depends on accurate analysis of the lower face and neck with attention to the contours and deep-lying structures. Although many surgeons address the well-recognized changes in skin and soft tissue that occur with aging, we believe bone resorption is also an important component. Loss of bone volume leads to loss of support for the soft tissues of the face. The result is soft tissue ptosis and loss of angularity between the various planes of the face. Initially, there is loss of the submental shadow and loss of height of the mandibular ramus. The gonial angle loses its prominence, and the chin becomes ptotic. The line of the body of the mandible is further obscured by the appearance of jowls. As the mandible shrinks, the submandibular gland as well as the muscles that make up the floor of the mouth are pushed inferiorly. For loss of bone support, implants tailored to the areas of deficit and to the aesthetic goals are used. These implants used for the mandible are tridimensional structures made from beaded polyethylene material. This restores the bone volume and provides good support for the soft tissues. We routinely perform a deep-layer cervicoplasty. This involves removing fat from the subplatysmal layer and between the anterior bellies of the digastric muscles. The digastric muscles are plicated toward the midline. The platysma muscle is separated from the underlying submandibular gland. Ptosis of the submandibular gland is treated by suspension of the fascia with sutures or imbrication of the overlying muscle. A short corset platysmaplasty brings the platysma muscles to the midline. Above the level of the hyoid bone, the digastric muscles are included in the sutures. If the patient has an obtuse cervicomental angle, but good-quality skin, there may be no need to perform skin resection. In these patients who are candidates for nonexcisional cervicoplasty, we routinely place a neck suspension suture. Patients with poor skin quality or excessive skin on the neck and jawline will require an excisional cervicoplasty or cervicofacial rhytidectomy. We have obtained consistently good results using this comprehensive approach.

Chin↗

PubMed2003

[Comprehensive evaluation of medical teaching -- a task for the psychosocial disciplines?].

The paper describes the experiences with a comprehensive evaluation of medical teaching at the medical faculty of the Friedrich-Schiller-University Jena. Based upon evaluations of courses initiated by the students, the evaluation of teaching is organized scientifically and extended as a comprehensive evaluation of several relevant issues (e. g. surveys of teachers and alumni) by the staff of the Department of Medical Psychology since 1998. Originally supported by a grant of the state of Thuringia, the evaluation is now financed by the medical faculty. The paper describes the requested resources for staff and material to establish a systematic evaluation of medical teaching. In addition, a detailed concept of the allocation of financial means considering evaluations, examinations, and other indicators of teaching quality is demonstrated. Based upon the results of studies related to the evaluation data base, the question of the establishment of an external evaluation in view of the coming changes of the medical curriculum in Germany is critically discussed.

Curriculum↗

PubMedDate not supplied

Low grade chiasmatic-hypothalamic glioma-carboplatin and vincristin chemotherapy effectively defers radiotherapy within a comprehensive treatment strategy -- report from the multicenter treatment study for children and adolescents with a low grade glioma -- HIT-LGG 1996 -- of the Society of Pediatric Oncology and Hematology (GPOH).

BACKGROUND: Low grade gliomas arise in all CNS-locations and age groups, chiasmatic-hypothalamic tumors occur especially in young children. Early radiotherapy (RT) shall be deferred by chemotherapy (CT) within the concept of the HIT-LGG 1996 study, offering a comprehensive treatment strategy for all age groups. PATIENTS: 198 of 905 protocol patients (21.9 %) had a chiasmatic (34), chiasmatic-hypothalamic (144) or hypothalamic (20) primary tumor, median age at diagnosis 3.6 years (0.2-16.3 y.), 54 had neurofibromatosis (27.3 %), 108 female (54.5 %). 98 children had severe visual impairment as their first symptom. The initial neurosurgical intervention resulted in 5 complete, 26 subtotal, 45 partial resections, 67 biopsies; 55 children had a diagnosis on the basis of neuroradiologic findings. Histology showed 132 pilocytic astrocytoma I degrees , 6 astrocytoma II degrees /nos and 2 DIGG/DIA I degrees (3 not known). RESULTS: 82 children were treated at diagnosis, 68 upon clinical or radiological progression following observation times of 3.0 to 115.0 months. RT: 27 children received conventional (18) or interstitial (8) RT (1 not documented) at a median age of 7.3 years; 7 tumors went into further progression. At a median observation time of 50.1 months 21 tumors are stable, 3 regressive (2 not evaluable, 1 death). CT: 123 children received vincristin/carboplatin at a median age of 3.7 years. 105/123 achieved CR/PR/SD. 44/123 tumors were progressive after median 22.5 months, 37 with a chiasmatic-hypothalamic primary, 16/44 were irradiated. At a median observation time of 44.7 months 2 children are in complete remission, 92 tumors are stable, 8 regressive, 9 progressive. 4 children died, 8 are not evaluable. At 60 months overall survival of the cohort is 0.93; PFS of the CT-group is 0.61, the RT-free survival 0.83. Within the CT-group children with an age at diagnosis < 1 year and non-pilocytic histology are at increased risk for early progression. Causative factors cannot be defined, yet. CONCLUSION: Within the comprehensive treatment strategy for low grade glioma HIT-LGG 1996 chemotherapy is effective to delay the need for early radiotherapy in chiasmatic-hypothalamic glioma. More effective reduction of the risk for progression has to be sought for young children < 1 year.

Adolescent↗

PubMed1985

The tendency to IUGR in preterm infants born to young women enrolled in a comprehensive prenatal program.

Low-birthweight infants born to young women in an urban poor and multiethnic community who attended an intensive comprehensive prenatal program were studied. Of the 801 young women followed, 69 (8.6%) delivered infants weighing less than or equal to 2500 gm. Despite comprehensive care, there was a high prevalence of maternal anemia though other obstetric factors were not significantly increased. Of the 69 low-birthweight infants, 82.6% were below the 50th percentile for weight. There was a tendency toward intrauterine growth retardation (IUGR) among preterm infants which was pronounced after 33 weeks gestation. Further studies are needed to determine what developmental insult could arrest growth and lead in some instances to preterm birth and in others to IUGR.

Adolescent↗

PubMedDate not supplied

[Language development disorders in childhood: nonverbal intelligence and language comprehension].

33 children with Specific Language Impairment (F 80, ICD 10) were randomly selected and their results regarding nonverbal intelligence, passive vocabulary and sentence comprehension were compared with data of 33 control children matched by age and sex. Although cognitive performance is average in both groups, significant differences regarding nonverbal intelligence are found. Whereas nonverbal intelligence is predictable from sentence comprehension to a high degree in den SLI-group, it is not predictable in the control group.

Austria↗

PubMed1982

Socioeconomic evaluation of a state-funded comprehensive hemophilia-care program.

To assess the effectiveness, cost, and socioeconomic gains associated with a comprehensive state-funded hemophilia program, we compared data from a three-year experience with such a program in Rhode Island with those from the preceding year. Self-treatment, integration of children into school, and achieving satisfying employment of adults are the main goals of the program. During the most recent year, 77 per cent of the patients with severe hemophilia in the state received total care through the Hemophilia Center. Twenty-eight of the 43 patients now treat themselves, the annual number of hospital days per patient has decreased from 12.6 to 3.5, and the number of visits to hospital facilities has fallen from 34 to 2.4, while the yearly cost of clotting factor per patient has remained about $7,000. Altogether, this has saved more than $10,000 each year for treatment, despite the cost of rehabilitative surgery. Numbers of days lost from school and work have decreased twofold and threefold, respectively. Best of all, comprehensive care has vastly improved the quality of life for patients with hemophilia in Rhode Island.

Adolescent↗

PubMed1995

A trial of annual in-home comprehensive geriatric assessments for elderly people living in the community.

BACKGROUND AND METHODS: The prevention of disability in elderly people poses a challenge for health care and social services. We conducted a three-year, randomized, controlled trial of the effect of annual in-home comprehensive geriatric assessment and follow-up for people living in the community who were 75 years of age or older. The 215 people in the intervention group were seen at home by gerontologic nurse practitioners who, in collaboration with geriatricians, evaluated problems and risk factors for disability, gave specific recommendations, and provided health education. The 199 people in the control group received their regular medical care. The main outcome measures were the prevention of disability, defined as the need for assistance in performing the basic activities of daily living (bathing, dressing, feeding, grooming, transferring from bed to chair, and moving around inside the house) or the instrumental activities of daily living (e.g., cooking, handling finances and medication, housekeeping, and shopping), and the prevention of nursing home admissions. RESULTS: At three years, 20 people in the intervention group (12 percent of 170 surviving participants) and 32 in the control group (22 percent of 147 surviving participants) required assistance in performing the basic activities of daily living (adjusted odds ratio, 0.4; 95 percent confidence interval, 0.2 to 0.8; P = 0.02). The number of persons who were dependent on assistance in performing the instrumental activities of daily living but not the basic activities did not differ significantly between the two groups. Nine people in the intervention group (4 percent) and 20 in the control group (10 percent) were permanently admitted to nursing homes (P = 0.02). Acute care hospital admissions and short-term nursing home admissions did not differ significantly between the two groups. In the second and third years of the study, there were significantly more visits to physicians among the participants in the intervention group than among those in the control group (mean number of visits per month, 1.41 in year 2 and 1.27 in year 3 in the intervention group, as compared with 1.11 and 0.92 visits, respectively, in the control group; P = 0.007 and P = 0.001, respectively). The cost of the intervention for each year of disability-free life gained was about $46,000. CONCLUSIONS: A program of in-home comprehensive geriatric assessments can delay the development of disability and reduce permanent nursing home stays among elderly people living at home.

Activities of Daily Living↗

PubMed2006

Comprehensive investigation of vibrational relaxation of non-hydrogen-bonded water molecules in liquids.

The vibrational dynamics of isolated water molecules dissolved in the nonpolar organic liquids 1,2-dichloroethane (C(2)H(4)Cl(2)) and d-chloroform (CDCl(3)) have been studied using an IR pump-probe experiment with approximately 2 ps time resolution. Analyzing transient, time, and spectrally resolved data in both the OH bending and the OH stretching region, the anharmonic constants of the bending overtone (v=2) and the bend-stretch combination modes were obtained. Based on this knowledge, the relaxation pathways of single water molecules were disentangled comprehensively, proving that the vibrational energy of H(2)O molecules is relaxing following the scheme OH stretch-->OH bend overtone-->OH bend-->ground state. A lifetime of 4.8+/-0.4 ps is determined for the OH bending mode of H(2)O in 1,2-dichloroethane. For H(2)O in CDCl(3) a numerical analysis based on rate equations suggests a bending overtone lifetime of tau(020)=13+/-5 ps. The work also shows that full 2-dimensional (pump-probe) spectral resolution with access to all vibrational modes of a molecule is required for the comprehensive analysis of vibrational energy relaxation in liquids.

Journal Article↗

PubMed1993

Limits on the comprehension of rotational motion: mental imagery of rotations with oblique components.

Mental imagery of rotational motion across variation in the orientation of a square to an axis of rotation, the orientation of the axis to the environment/viewer, and the starting orientation of the rotation were investigated in three experiments. The experimental method included specifying the particular rotations that subjects should consider and obtaining exact predictions of the outcomes of the rotations. When the square was normal to the axis and the axis was normal to the environment/viewer, performance was excellent. When either of these relationships was oblique, performance was quite good. When both of these relationships were oblique, nearly every subject made large errors on every problem. The difficulty of the double-oblique rotations was reduced when the initial orientation of the square was not canonical. Current views of the comprehension of rotational motion are discussed. It appears that the comprehension of rotational motion can be understood as an organizaiton of the symmetric space traced out by the motion. People succeed in organizing this space when it is aligned with a principal spatial reference system.

Adult↗

PubMed2001

A comprehensive two-hybrid analysis to explore the yeast protein interactome.

Protein-protein interactions play crucial roles in the execution of various biological functions. Accordingly, their comprehensive description would contribute considerably to the functional interpretation of fully sequenced genomes, which are flooded with novel genes of unpredictable functions. We previously developed a system to examine two-hybrid interactions in all possible combinations between the approximately 6,000 proteins of the budding yeast Saccharomyces cerevisiae. Here we have completed the comprehensive analysis using this system to identify 4,549 two-hybrid interactions among 3,278 proteins. Unexpectedly, these data do not largely overlap with those obtained by the other project [Uetz, P., et al. (2000) Nature (London) 403, 623-627] and hence have substantially expanded our knowledge on the protein interaction space or interactome of the yeast. Cumulative connection of these binary interactions generates a single huge network linking the vast majority of the proteins. Bioinformatics-aided selection of biologically relevant interactions highlights various intriguing subnetworks. They include, for instance, the one that had successfully foreseen the involvement of a novel protein in spindle pole body function as well as the one that may uncover a hitherto unidentified multiprotein complex potentially participating in the process of vesicular transport. Our data would thus significantly expand and improve the protein interaction map for the exploration of genome functions that eventually leads to thorough understanding of the cell as a molecular system.

Fungal Proteins↗

PubMed2001

Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer.

The biological significance of DNA amplification in cancer is thought to be due to the selection of increased expression of a single or few important genes. However, systematic surveys of the copy number and expression of all genes within an amplified region of the genome have not been performed. Here we have used a combination of molecular, genomic, and microarray technologies to identify target genes for 17q23, a common region of amplification in breast cancers with poor prognosis. Construction of a 4-Mb genomic contig made it possible to define two common regions of amplification in breast cancer cell lines. Analysis of 184 primary breast tumors by fluorescence in situ hybridization on tissue microarrays validated these results with the highest amplification frequency (12.5%) observed for the distal region. Based on GeneMap'99 information, 17 known genes and 26 expressed sequence tags were localized to the contig. Analysis of genomic sequence identified 77 additional transcripts. A comprehensive analysis of expression levels of these transcripts in six breast cancer cell lines was carried out by using complementary DNA microarrays. The expression patterns varied from one cell line to another, and several overexpressed genes were identified. Of these, RPS6KB1, MUL, APPBP2, and TRAP240 as well as one uncharacterized expressed sequence tag were located in the two common amplified regions. In summary, comprehensive analysis of the 17q23 amplicon revealed a limited number of highly expressed genes that may contribute to the more aggressive clinical course observed in breast cancer patients with 17q23-amplified tumors.

Breast Neoplasms↗